During fiscal year 2009, we accomplished the following: 1. Demonstrated that tonic BCR signaling that leads to the de novo synthesis of p100 (NFKB2 protein) requires the activity of phosphotidylinositol-3-kinase (PI3K). p100 up-regulation, upon ex vivo culture, was blocked in splenic B cells from p110delta-deficient mice, and in B cells from wild-type mice cultured in the presence of PI3K inhibitors. Downstream of PI3K, Brutons tyrosine kinase (Btk) was required for p100 up-regulation. 2. The signal from BCR was transmitted to PI3K via the adapter molecule BCAP. BCAP-deficient B cells did not up-regulate p100 protein in response to tonic or acute BCR activation. 3. We obtained preliminary evidence that the function of PI3K was at a post-transcriptional step. Specifically, LY294002 blocked p100 protein production without affecting p100 mRNA in response to BCR cross-linking. Moreover, p100 mRNA levels decreased over the time-course of ex vivo culture, while p100 protein levels increased over the same time period. We are currently investigating the mechanism of post-transcriptional control of de novo p100 synthesis.